This application is based on Japanese Patent Application Nos. 2000-374852 and 2001-305231 filed in Japan on Dec. 8, 2000 and Oct. 1, 2001, respectively, the entire contents of which are hereby incorporated by reference.
The present invention relates to a particle separation mechanism. In one embodiment, the present invention relates to a particle separation mechanism which can be used to separate particles contained in a solution.
Recent attention has focused on xcexc-TAS (micro total analysis system) for miniaturizing devices for use in various processes of chemical analysis and synthesis and the like, and for applications to micromachine art.
For example, there is a concept of a separation system using xcexc-TAS for separating particles contained in a solution. A microstructure is formed in a flow pass by micro processing art, and loaded in a polymer gel to form a filter for separating particles by size.
In this case, the filter is formed from the bottom surface to the top surface of a flow pass, over the entire cross section of the flow pass. For this reason, when particles are separated by the filter, and a pump is used to provide the propulsion force for the solution containing the particles, the size of the holes of the filter generally used for separation (which can range from sub micron level to approximately 30 xcexcm) are too small and increase the flow pass resistance, such that it is difficult for the solution to pass through the filter.
Furthermore, when a solution passes through a filter having relatively large holes, the solution being propelled via a pump which generates an extremely strong pressure, although particle separation is initially possible, eventually the separated particles block the holes of the filter, thereby greatly increasing the flow pass resistance such that the solution cannot be transported.
Accordingly, a problem of the art to be resolved by the present invention is to provide a particle separation mechanism capable of efficient and continuous particle separation.
To resolve the previously mentioned problems of the art, one embodiment of the present invention provides a microchip having a particle separation mechanism with the structure described below.
The microchip comprises a flow pass in which a solution containing particles can flow, and a particle separation mechanism. The particle separation mechanism comprises a deflection mechanism, which generates an electric field or magnetic field in a transverse direction of the flow pass. The field is generated in a deflection region of the flow pass so as to alter a direction of flow of the particles. The particle separation mechanism further comprises a particle capture unit disposed on a side of the flow pass to which the particles are directed by the deflecting mechanism so as to capture the particles.
In this structure, as the particles in the solution flowing through the flow pass approach the deflection region, the particles are directed to one side of the flow pass. The direction of flow of the particles is deflected in the direction of an electric field or a magnetic field (or in a direction opposite the electric field or the magnetic field) by the deflection mechanism. The particles can thus be captured by the particle capture unit disposed at this location. In this way, the desired particles can be separated from a solution containing the particles.
According to this structure, an electric field or magnetic field is generated in a direction transverse to the flow pass to separate the particles. Since a direction transverse to the flow pass (e.g., the width direction or the height direction of the flow pass) has an extremely small dimension when compared to the length direction of the flow pass, only a small voltage or magnetic force is required to generate a desired electric field or magnetic field.
Accordingly, a structure generating a relatively low electric field or magnetic field may be used as the deflection mechanism, such that the particle separation mechanism can be made compact and inexpensive.
Specifically, the particle capture unit may be structured in various embodiments as described below.
In a first embodiment, it is desirable that the particle capture unit include a projection. The projection has a radix end on a surface on the deflection side of a surface forming the flow pass. The projection partially extends into the flow pass and thus occupies only a part of the cross section of the flow pass.
In this structure, the projection of the particle capture unit is disposed on one side of the flow pass (the deflection side) in a direction traverse to a direction of flow of the flow pass. The particles in the solution are attracted by the electric field or the magnetic field, and are captured on the projection. The particles accumulated on the particle capture unit are released from the particle capture unit by, for example, the deflection mechanism generating an electric field or a magnetic field in the opposite direction, and are collected when they flow downstream.
According to this structure, since the particle capture unit does not have exclusive possession of the entire outflow cross section of the flow pass, and is only disposed in a portion of the deflection side of the flow pass, the captured particles do not block the entire cross section of the flow pass, and do not hinder the flow of the solution. Accordingly, continuous, efficient particle separation occurs.
The projection may have an optional form. For example, the projection may be a plate extending in a direction transverse to a direction of flow of the flow pass. Alternatively, an indentation may be formed by circumscription by the projection, such that this indentation opens to the center of the flow pass. In order to efficiently capture particles, it is desirable that a plurality of columnar projections are provided, such that a solution flows among the columns.
It is desirable that the particle capture unit includes a plurality of columnar projections. In one embodiment, the space between adjacent projections is 0.1 xcexcm or more, but less than 50 xcexcm.
This structure is suitable for extracting blood plasma components by attracting erythrocytes, leukocytes, and thrombocytes to the projections for removal from whole blood.
In a second embodiment, the flow pass includes a single main flow pass on the upstream side (in the direction of flow), and includes two or more branch flow passes branching from the main flow pass in the downstream direction (in the direction of flow). In this case, the deflection region is near the junction (branch point) of the main flow pass and the branch flow passes, and a deflection mechanism is provided with electrodes (or other types of field generators) in or near each branch flow pass and proximate the junction (branch point). In a more specific embodiment, the branch flow passes are arranged so as to be between the electrodes.
In this embodiment, in one branch flow pass, voltages of different electrical potentials are applied to the electrodes, which are arranged on bilateral sides of the branch flow pass, with the branch flow pass therebetween. The electrodes generate an electric field in a transverse direction to the branch flow pass. In the other branch flow pass, however, voltages of identical electric potential are applied to the electrodes, which are arranged on bilateral sides of the branch flow pass, with the branch flow pass therebetween. In this way, particles in the solution are attracted to the branch flow pass in which an electric field is generated in the transverse direction of the branch flow pass, so as to flow into this branch flow pass.
In this structure, voltages of different electric potential are applied to electrodes disposed bilaterally on the branch flow passes, such that the branch flow pass in which the electric field is generated in a transverse direction of the branch flow pass can selectively become the particle capture unit.
According to this structure, particle extraction is simple since captured particles flow through the branch flow pass. Moreover, particles may be continuously collected, such that a special operation is unnecessary to remove the particles accumulated by the particle capture unit.
It is desirable that the electrodes are formed as low resistance parts doped with a high concentration of an impurity on a silicon substrate. The flow pass is formed by partially removing the region doped with the impurity on the substrate via an etching process.
According to this structure, the microchip having flow passes (main flow pass and branch flow passes) and electrodes can be easily and efficiently manufactured using a micromachining process.
Furthermore, a microchip in accordance with another embodiment of the present invention is provided with a flow pass in which a solution containing particles can flow, and a particle separation mechanism. The particle separation mechanism comprises a filter (particle capture unit), including projections, each having a radix end on one side of the surface forming the flow pass. Only a part of the projections, which forms the filter, has exclusive possession of the side surface in a cross section of the flow pass.
According to this structure, since the particle capture unit does not have exclusive possession of the entire outflow cross section and is only disposed at part of the other side of the flow pass, the captured particles do not block the entire cross section direction of the flow pass, and do not hinder the flow of the solution. Accordingly, continuous, efficient particle separation occurs.
Various structures may be used as the filter. For example, the filter may be a microstructure formed within the flow pass using a micromachining process, porous glass or porous silicon may be adhered to a wall surface of the flow pass, or an anode may be formed on the wall surface of the flow pass.
A microchip in accordance with another embodiment of the present invention comprises a main flow pass in which a solution containing particles can flow, and a particle separation mechanism. The particle separation mechanism comprises a first branch flow pass and a second branch flow pass branching from the main flow pass. The first and second branch flow passes are disposed on the downstream side of the main flow pass. The particle separation mechanism further comprises a first electrode pair disposed with the first branch flow pass therebetween near the branch point with the main flow pass, and a second electrode pair disposed with the second branch flow pass therebetween near the branch point with the main flow pass.
In this embodiment, in one branch flow pass, voltages of different electrical potentials are applied to the electrode pair, which are arranged on bilateral sides of the branch flow pass, so as to generate an electric field in the transverse direction of the branch flow pass. In the other branch flow pass, however, voltages of identical electrical potentials are applied to the electrode pair, which are arranged on bilateral sides with the branch flow pass therebetween. In this way, particles in the solution are attracted to the branch flow pass in which an electric field is generated in the transverse direction of the branch flow pass, so as to flow into this branch flow pass.
One electrode of the first electrode pair and one electrode of the second electrode pair may be used in common, thereby simplifying the electrode structure.
The first and second electrode pairs may be formed by doping a high concentration of an impurity on a silicon substrate, and the flow pass may be formed by partially removing the region doped with an impurity on the substrate by an etching process.
In any of the aforesaid microchips, a micropump may be provided to produce the flow of a solution containing particles through the flow pass.
Each embodiment of the particle separation mechanism is suitable for use in a particle separation device for separating particles from a solution. In one embodiment, the particle separation device is provided with a micropump drive circuit for driving the micropump of the particle separation mechanism, a deflection control circuit for driving the deflection mechanism (or a voltage circuit for applying a voltage to the electrode), and a control circuit for controlling the operation of the micropump drive circuit and the deflection control circuit or voltage circuit.
The present invention further provides the particle separation method described below.
The particle separation method is a method of the type for separating particles from a solution using a particle separation mechanism. One embodiment of the particle separation method comprises a first step of producing a flow of a solution containing particles through a flow pass, a second step of forming an electric field or magnetic field in a direction transverse to the flow pass in a deflection region and deflecting or attracting particles within the solution flowing through the flow pass to one side surface of the flow pass (the deflection surface), and a third step of capturing the particles attracted to the side surface by a microstructure formed on the side surface.
The present invention further provides a particle separation method described below.
The particle separation method is a method of the type for separating particles from a solution using a particle separation mechanism. One embodiment of the particle separation method comprises a first step of producing a flow of a solution containing particles through a flow pass including a main flow pass and a plurality of branch flow passes branching from the main flow pass, a second step of setting to a desired electric or magnetic potential the bilateral side surfaces of a branch flow pass for each branch flow pass near the branching part of the flow pass, and a third step of deflecting or attracting particles within the solution flowing in the flow pass to one or another of the branch flow passes so as to flow through that branch flow pass by means of an electric field or magnetic field formed by the potential set in the second step.